Department of Pulmonary and Critical Care Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, China.
The Second Clinical Mediccal college, Shanxi Medical University, Taiyuan, China.
Front Cell Infect Microbiol. 2024 May 22;14:1348685. doi: 10.3389/fcimb.2024.1348685. eCollection 2024.
The microbiota-gut-lung axis has elucidated a potential association between gut microbiota and idiopathic pulmonary fibrosis (IPF). However, there is a paucity of population-level studies with providing robust evidence for establishing causality. This two-sample Mendelian randomization (MR) analysis aimed to investigate the causal relationship between the gut microbiota and IPF as well as lung function.
Adhering to Mendel's principle of inheritance, this MR analysis utilized summary-level data from respective genome-wide association studies (GWAS) involving 211 gut microbial taxa, IPF, and lung function indicators such as FEV, FVC, and FEV/FVC. A bidirectional two-sample MR design was employed, utilizing multiple MR analysis methods, including inverse variance-weighted (IVW), weighted median, MR-Egger, and weighted mode. Multivariable MR (MVMR) was used to uncover mediating factors connecting the exposure and outcome. Additionally, comprehensive sensitivity analyses were conducted to ensure the robustness of the results.
The MR results confirmed four taxa were found causally associated with the risk of IPF. (OR=0.773, 95% CI: 0.610-0.979, p=0.033), (OR=0.773, 95% CI: 0.610-0.979, p=0.033), and (OR=0.793, 95% CI: 0.652-0.965, p=0.020) exerted protective effects on IPF, while (OR=1.349, 95% CI: 1.021-1.783, p=0.035) promote the development of IPF. Several taxa were causally associated with lung function, with those in , and being the most prominent beneficial microbiota, while those in , and were associated with impaired lung function. As for the reverse analysis, MR results confirmed the effects of FEV and FVC on the increased abundance of six taxa (, and ) with a boosted level of evidence. MVMR suggested monounsaturated fatty acids, total fatty acids, saturated fatty acids, and ratio of omega-6 fatty acids to total fatty acids as potential mediating factors in the genetic association between gut microbiota and IPF.
The current study suggested the casual effects of the specific gut microbes on the risk of IPF and lung function. In turn, lung function also exerted a positive role in some gut microbes. A reasonable dietary intake of lipid substances has a certain protective effect against the occurrence and progression of IPF. This study provides novel insights into the potential role of gut microbiota in IPF and indicates a possible gut microbiota-mediated mechanism for the prevention of IPF.
肠道微生物群-肠道-肺轴阐明了肠道微生物群与特发性肺纤维化（IPF）之间可能存在关联。然而，提供强有力的证据来确定因果关系的人群水平研究仍然很少。本项两样本孟德尔随机化（MR）分析旨在研究肠道微生物群与 IPF 以及肺功能之间的因果关系。
本 MR 分析遵循孟德尔遗传法则，利用涉及 211 种肠道微生物类群、IPF 和肺功能指标（如 FEV、FVC 和 FEV/FVC）的各自全基因组关联研究（GWAS）的汇总水平数据。采用双向两样本 MR 设计，使用多种 MR 分析方法，包括逆方差加权（IVW）、加权中位数、MR-Egger 和加权模式。多变量 MR（MVMR）用于揭示连接暴露和结果的中介因素。此外，还进行了全面的敏感性分析以确保结果的稳健性。
MR 结果证实有 4 种微生物类群与 IPF 的发病风险存在因果关系。（OR=0.773，95%CI：0.610-0.979，p=0.033）、（OR=0.773，95%CI：0.610-0.979，p=0.033）和（OR=0.793，95%CI：0.652-0.965，p=0.020）对 IPF 具有保护作用，而（OR=1.349，95%CI：1.021-1.783，p=0.035）则促进了 IPF 的发生。有几种微生物类群与肺功能存在因果关系，其中属于 、和的微生物类群具有最显著的有益作用，而属于 、和的微生物类群则与肺功能受损相关。至于反向分析，MR 结果证实 FEV 和 FVC 对 6 种微生物类群（、和）丰度增加的影响，其证据水平有所提升。MVMR 表明单不饱和脂肪酸、总脂肪酸、饱和脂肪酸以及ω-6 脂肪酸与总脂肪酸的比例可能是肠道微生物群与 IPF 之间遗传关联的潜在中介因素。
本研究提示特定肠道微生物群对 IPF 风险和肺功能的因果作用。反过来，肺功能对某些肠道微生物群也有积极作用。合理摄入脂类物质对 IPF 的发生和进展具有一定的保护作用。本研究为肠道微生物群在 IPF 中的潜在作用提供了新的见解，并表明了一种预防 IPF 的可能的肠道微生物群介导机制。
